Differential anterograde transport of HSV type 1 viral strains in the murine optic pathway

Differential anterograde transport of HSV type 1 viral strains in the murine optic pathway
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DOI:
10.3109/13550289909021996
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发表时间:
1999-04-01
影响因子:
3.2
通讯作者:
LaVail, JH
LaVail, JH
中科院分区:
医学4区
文献类型:
--
作者:
Garner, JA;LaVail, JH

文献摘要

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单纯疱疹病毒1型(HSV-I)在神经元中的主动顺行转运通常是基于原发性感染细胞的突触后靶细胞中感染的早期出现而假定的,并且通过基于微管马达的逆行转运机制的良好证据进一步逻辑推断。然而,新合成的病毒在中枢神经系统神经元中的顺行运动机制的直接证据实际上尚未获得。在研究后者的努力中,我们将得到病毒株的极大帮助,这些病毒株在顺行方向上的移动能力存在差异。我们比较了三个HSV株(F株,H129和MacIntyre B)在小鼠视觉系统中的顺行轴突运输。在BALB/c小鼠中眼内注射等滴度的病毒。从接种后2-6天,收获感染的视神经通路的节段,并使用抗HSV多克隆抗体进行蛋白质印迹。H129非常迅速地向终末移动(接种后3天)。F株的扩散速度比H129慢,但也在4天前到达终末区,MacIntyre B仅在最近端视神经中聚集,5天后仅在远端视神经中可见非常微弱的分布。巧合的是,在MacIntyre B中,单个病毒蛋白的表达似乎大大减少。我们的研究结果表明,不同的病毒株显示其顺行传播能力的变异性,这些菌株的进一步比较可能会揭示病毒如何参与宿主细胞的运输机制。
Active anterograde transport of herpes simplex virus Type 1 (HSV-I) in neurons is often assumed based on early appearance of infection in postsynaptic target cells of a primary infected cell, and is further logically inferred by good evidence of microtubule-motor based mechanisms of retrograde transport. However, direct evidence of mechanisms of anterograde movement of newly synthesized virus in CNS neurons actually has yet to be obtained. In efforts to investigate the latter, we will be greatly aided by viral strains that exhibit differences in their ability to move in an anterograde direction. We compared the anterograde axonal transport of three HSV strains (F strain, H129, and MacIntyre B) in the murine visual system. Equivalent titers of virus were injected intraocularly in BALB/c mice. From 2-6 days after inoculation, segments of the infected optic pathway were harvested and Western blots using an anti-HSV polyclonal antibody performed. H129 traveled very rapidly towards the terminals (3 days post-inoculation). F strain spread more slowly than H129, but also reached terminal regions by 4 days, MacIntyre B accumulated only in the most proximal optic nerve, and was seen only very faintly in distal optic pathway after 5 days. Coincidentally, a single viral protein appeared to be greatly reduced in expression in MacIntyre B. Our results suggest that different viral strains display variability in their capacity to spread anterogradely, and that further comparison of these strains may reveal how virus engages the host cell transport machinery.